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Adv Healthc Mater. 2018 Oct;7(19):e1800488. doi: 10.1002/adhm.201800488. Epub 2018 Aug 8.

Human Corneal Tissue Model for Nociceptive Assessments.

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Department of Biomedical Engineering, Tufts University, 4 Colby Street, Medford, MA, 02155, USA.
School of Medicine, Departamento de Oftalmologia da Escola Paulista de Medicina, Federal University of São Paulo, Botucatu, 822 - Vila Clementino, São Paulo, -SP, 04023-062, Brazil.
New England Eye Center, Tufts Medical Center, 260 Tremont St, 9th Floor, Boston, MA, 02111, USA.
Eye & Ear Institute, Department of Ophthalmology, University of Pittsburgh, 203 Lothrop Street, Room 1011, Pittsburgh, PA, 15213, USA.


New in vitro tissue models to mimic in vivo conditions are needed to provide insight into mechanisms involved in peripheral pain responses, potential therapeutic strategies to address these responses, and to replace animal models for such indications. For example, the rabbit cornea Draize test has become the standard method used for decades to screen ophthalmic drug and consumer product toxicity. In vitro tissue models with functional innervation have the potential to replace in vivo animal testing and provide sophisticated bench tools to study ocular nociception and its amelioration. Herein, full thickness, innervated, 3D human corneal tissues are grown under physiologically relevant culture conditions to study nociceptive-related responses, by mimicking ocular environmental cues, including intraocular pressure (IOP) and tear flow (TF). Capsaicin, a chili pepper-derived irritant known to cause a burning sensation in mammalian tissues is utilized as a nociceptive stimulant to induce pain, while subsequent serum treatment is used to mimic healing. Pain mediators released upon capsaicin stimulation and cell regrowth after serum treatment are characterized to assess ocular responses in this new, innervated, human corneal tissue system for comparison of outcomes to established animal and related responses.


corneas; in vitro tissue models; innervation; pain; silk


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